The principal objectives of this renewal proposal are: (A) the development of an effective and stereochemically controlled synthesis of both racemic and optically active bay-region diol epoxides of phenanthrene, benz(a)anthracene, and 7,12-dimethyl benz(a)anthracene, (B) the study of the chemical properties and reactivities of the diol epoxide metabolites of carcinogenic aromatic hydrocarbons such as benz(a)anthracene and 7,12-dimethylbenz(a)anthracene and the elucidation of the structures of the reaction products of these hydrocarbons and their diol epoxide derivatives with nucleic acids in vivo and in vitro, respectively, and (C) the elucidation of the molecular mechanism of the epoxide hydrase reactions with arene oxides. Efforts towards the synthesis of bay-region diol epoxides will involve the use of various modifications of Diels-Alder reactions. Optical resolution of diol epoxides will be performed with the aid of high pressure liquid chromatography. The absolute configurations of the natural metabolites which can also be prepared from resolved precursors will be determined employing the exciton chirality circular dichroism method. The molecular geometries of bay-region diol epoxides will be studied using C-13 spin lattice relaxation times and x-ray analysis in order to ascertain the existence of intramolecular hydrogen bonding in one of the diastereomers. Efforts will be made to correlate this interaction with the relative reactivities of each diastereomeric diol epoxide. The reactions of diol epoxides with various nucleophiles will be performed to obtain information on the stabilities of the possible bay-region and non-bay region benzylic carbonium ions which may serve as a possible index for the actual carcinogenicity of various diol epoxides. The extent of diol epoxide binding to the phosphate backbone and nucleic acid bases will be studied using various synthetic and natural nucleic acids.